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Determination of treatment modalities for diabetic retinopathy and diabetic maculopathy -Strategic approach using molecular and cellular biological methods-

确定糖尿病视网膜病变和糖尿病黄斑病变的治疗方式 -使用分子和细胞生物学方法的策略方法-

基本信息

批准号：
15591841
负责人：
YAMASHITA Hidetoshi
金额：
$ 2.24万
依托单位：
Yamagata University Faculty of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591841/
关键词：
Diabetic retinopathy VEGF IL-6 oxidative stress 8-OHdG NOx severity of diabetic retinopathy SNPs 重症度判定 OCT 遺伝子 SNPs DGKs

项目摘要

Various factors are involved in the pathogenesis of diabetic retinopathy and diabetic maculopathy (macular edema). The candidates of the risk factors are factors related to oxidative stress and retinal angiogenesis. As the first step, to investigate the candidate molecules to play important roles in diabetic retinopathy, the expression levels of the bio-marker of cell damage due to oxidative stress ((8-OHdG and NOx) and cytokines (VEGF and IL-6) were measured in the vitreous humor obtained from the diabetic eyes after securing the written permission. This study was approved by the ethical committee of Yamagata University Faculty of Medicine. This study has revealed that the diabetic retinopathy and the diabetic maculopathy are closely related to the oxidative stress and VEGF, IL-6. As the second step, to investigate the molecular pathogenesis of diabetic retinopathy by focusing the retinal damage to retinal neurons, the intracellular signal transduction of hyperglycemia, including abno … More rmal metabolic pathways and cytokine expression acceleration, has been investigated using the in vitro systems. This study has revealed that diacylglycerol activates protein kinase C, which increases VEGF expression in retinal cells.Taken together, VEGF is one of the main factors to be involved in the pathogenesis of diabetic retinopathy and maculopathy. One of the single nucleotide polymorphisms (SNPs) in the VEGF gene was investigated. The frequencies of VEGF +813 C-T (CC, CT, TT) were determined in DNA from 108 subjects (non DM=12 subjects, DM=96 subjects). The frequencies of the VEGF +813 C_T polymorphisms were similar in both DM and non DM groups. The severity of retinopathy was not related to VEGF +813 polymorphism. The results of this study have revealed that the expression levels of cytokines and oxidative stress related factors, not the genetic factor were related to diabetic retinopathy and maculopathy. It is mandatory to search for the more useful factors relevant to diabetic retinopathy and maculopathy to set up the system to determine the treatment modalities for diabetic retinopathy and maculopathy. Less

糖尿病视网膜病变和糖尿病黄斑病变（黄斑水肿）的发病机制涉及多种因素。危险因素的候选者是与氧化应激和视网膜血管生成相关的因素。作为第一步，为了研究在糖尿病视网膜病变中起重要作用的候选分子，在获得书面许可后，在从糖尿病眼睛获得的玻璃体液中测量由于氧化应激（（8-OHdG和NOx））和细胞因子（VEGF和IL-6）引起的细胞损伤的生物标志物的表达水平。本研究已获得山形大学医学部伦理委员会的批准。本研究揭示糖尿病视网膜病变和糖尿病黄斑病变与氧化应激和VEGF、IL-6密切相关。第二步，从视网膜神经元的损伤、高血糖的细胞内信号转导、abno信号转导等方面探讨糖尿病视网膜病变的分子发病机制。 ...更多信息正常代谢途径和细胞因子表达加速，已经使用体外系统进行了研究。本研究发现，甘油二酯激活蛋白激酶C，使视网膜细胞VEGF表达增加，VEGF是糖尿病视网膜病变和黄斑病变的主要致病因子之一。研究了VEGF基因中的一个单核苷酸多态性（SNP）。在108例受试者（非DM=12例，DM=96例）的DNA中测定VEGF +813 C-T（CC，CT，TT）的频率。VEGF +813 C_T多态性在DM组和非DM组中的分布频率无显著性差异。视网膜病变的严重程度与VEGF +813基因多态性无关。本研究结果提示细胞因子和氧化应激相关因子的表达水平与糖尿病视网膜病变和黄斑病变相关，而与遗传因素无关。寻找与糖尿病视网膜病变和黄斑病变相关的更有用的因素以建立系统来确定糖尿病视网膜病变和黄斑病变的治疗方式是强制性的。少